The present disclosure relates generally to a method of altering metabolism of a dietary nutrient (e.g., phosphate) in livestock via an antibody, which increases the absorption and retention of the dietary nutrient, thereby decreasing its excretion into the environment.
Fibroblast growth factor-23 (FGF-23) has recently been identified as a major player in phosphate homeostasis. (See Liu and Quarles, “How Fibroblast Growth Factor 23 works,” J. Am. Soc. Nephrol. 18:1637-1647 (2007) and Yamashita et al., “Identification of a novel fibroblast growth factor, FGF-23, preferentially expressed in the ventrolateral thalamic nucleus of the brain,” Biochem. Biophys. Res. Commun. 277:494-498 (2000)). FGF-23 is predominately produced by osteocytes in bone, and its principal actions are to inhibit sodium-dependent phosphate reabsorption and 1α-hydroxylase activity in the kidney, leading to increased phosphate excretion and low circulating 1,25(OH)2D3 levels (hence reduced intestinal absorption of phosphate). (See Liu and Quarles, “How Fibroblast Growth Factor 23 works,” J. Am. Soc. Nephrol. 18:1637-1647 (2007) and Liu et al., “Emerging role of fibroblast growth factor 23 in a bone-kidney axis regulating systemic phosphate homeostasis and extracellular matrix mineralization,” Curr. Opin. Nephrol. Hypertens. 16:329-335 (2007)). It has been suggested that FGF-23 behaves as a counter regulatory hormone for 1,25(OH)2D3, which maintains phosphate balance in the presence of vitamin D-mediated suppression of parathyroid hormone and increased intestinal phosphate and calcium absorption. Low levels of FGF-23 are detected in circulation in normal individuals; however, levels are increased in response to phosphate loading, vitamin D administration, renal failure, and in hereditary and acquired hypophosphate homeostasis and mineralization. (See Liu and Quarles, “How Fibroblast Growth Factor 23 works,” J. Am. Soc. Nephrol. 18:1637-1647 (2007) and Stubbs et al., “Role of Fibroblast Growth Factor 23 in Phosphate Homeostasis and Pathogenesis of Disordered Mineral Metabolosm in Chronic Kidney Disease,” Seminars in Dialysis 20:302-308 (2007)).
Phosphate homeostasis and excretion is of particular interest in agriculture. Phosphate is typically fed above the animal's requirement to promote growth in an animal, particularly a livestock. Circulatory phosphate levels above the immediate needs of the animal are rapidly excreted by action of FGF-23. Not only is excess phosphate that is excreted by the animal an environmental concern but excreted phosphate is also costly to the producer because of the high cost of phosphate supplements used for animal growth. Discovery of means to improve the retention of phosphate by the animal would decrease the need to add expensive phosphate to the animal's diet and would reduce phosphate contamination of the environment from animal excreta. (See Ward, “Phosphorus-friendly transgenics,” Nature Biotechnology, 19:415-416 (2001)).
Accordingly, there is a need for methods of altering the metabolism of dietary phosphate in animals such to increase phosphate availability and absorption, thereby reducing the amount of phosphate required for administration in animals.